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. Author manuscript; available in PMC: 2025 Apr 1.
Published in final edited form as: Am J Ophthalmol. 2023 Dec 22;260:190–199. doi: 10.1016/j.ajo.2023.12.008

Extending Peripheral Retinal Vascularization in Retinopathy of Prematurity (ROP) through Regulation of VEGF Signaling

Lydia Sauer 1, Melissa Chandler 1, M Elizabeth Hartnett 1,2,*
PMCID: PMC10981561  NIHMSID: NIHMS1954094  PMID: 38141904

Abstract

Purpose:

Experimental studies provide evidence that regulation of VEGF receptor-2 signaling in endothelial cells orders cell divisions and extends developmental angiogenesis, while inhibiting pathologic intravitreal angiogenesis and has relevance to retinopathy of prematurity (ROP). We tested the hypothesis that intravitreal anti-VEGF would extend vascularization into peripheral avascular retina in human type 1 ROP compared to controls.

Design:

Retrospective, non-randomized treatment comparison

Methods:

Setting:

Academic institution

Study population:

All premature infants screened for ROP from January 2019 through December 2022. The experimental group included type 1 ROP treated with bilateral bevacizumab (0.25mg) and had adequate fundus imaging by a certified ophthalmic photographer at two examinations: within 2 weeks of treatment and 1–3 weeks later. A control group included gestational age- and birthweight-matched infants with ROP less severe than type 1 ROP.

Main outcome measure:

Extent of temporal retinal vasculature measured by a masked analyst between treated and control eyes. Paired and non-paired t-tests were used.

Results:

Of 382 screened infants, 34 developed type 1 ROP; 11 comprised the experimental group and 11 the control group. At baseline, there was a trend toward shorter temporal vascular extent in treatment compared with control groups (3667±547 pixels vs. 4262±937 pixels, CI −1277px;88px, p=0.084) but no difference between groups at follow-up (p=0.945). Vascular extension was significantly greater in the treatment than control, (872±521px vs. 253±151px, CI 262px;977px, p=0.003) showing catch-up growth.

Conclusions:

This clinical evidence supports laboratory-based studies that regulation of VEGF using an intravitreal anti-VEGF agent increases developmental angiogenesis into the peripheral avascular retina while inhibiting pathologic intravitreal angiogenesis in ROP.

Keywords: angiogenesis, VEGF, retinopathy of prematurity, bevacizumab, anti-VEGF, peripheral avascular retina, ROP

Table of Contents Statement

Using color images, the authors show anti-VEGF in type 1 ROP extends peripheral retinal vascularization to a greater degree than untreated non-type 1 ROP, providing clinical support for experimental studies in which dysregulated VEGF disordered developmental angiogenesis as in stage 3 ROP. A method to quantify vascular extent was used. Infants in treatment and control groups were matched by prematurity. Imaging was with the same camera, photographer and analyzed by the same masked analyst.

INTRODUCTION

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness and has increased worldwide, including in the US where the incidence has doubled over the last decade.1,2 ROP is described in sequential phases, in which first avascular retina from damaged newly developed vessels and delayed developmental retinal vascularization, stimulates the production of an angiogenic factor or factors that then cause abnormal intravitreal (i.e., extraretinal) neovascularization at the junctions of vascular and avascular retina.3–6 Initially, oxygen monitoring and regulation were identified as important to reduce the development of ROP, but as infants have survived greater extremes of prematurity, ROP has persisted and become more prevalent.7,8

Treatments for ROP have also evolved from cryotherapy to laser destruction of the peripheral avascular retina and now to anti-angiogenic agents, most notably those that interfere with the bioactivity of vascular endothelial growth factor (VEGF).9–13 Proof of concept was shown experimentally that regulating the angiogenic signaling pathway of VEGF specifically through VEGF receptor-2 in retinal endothelial cells not only inhibited intravitreal neovascularization, but also extended vascularization into the peripheral avascular retina.14 This finding differs from adult vitreoretinal diseases, in which retinal vascular development is complete and the effect of VEGF regulation is minimal on vascularizing avascular retina. The extension of peripheral vascularization would be desirable to potentially expand visual field and reduce the stimulus for reactivated ROP.15 However, the finding that an inhibitor of VEGF, which itself is an angiogenic factor important in retinal vascular development, would support retinal vascular growth was unpredicted, because inhibition of angiogenesis was expected to inhibit both physiologic and pathologic angiogenesis. Intravitreal compounds that bind VEGF and interfere with receptor binding have been used to regulate VEGF receptor-2 signaling, but these are not specific to the type of retinal cell or VEGF receptor. Although some intravitreal anti-VEGF agents are associated with regression of ROP and vascularization into the peripheral avascular retina, including reports using fluorescein angiography,16 other reports show vascular growth arrest with some agents and doses, or persistent avascular retina (PAR).17

Endothelial cell-specific knockdown of VEGF receptor-2 administered with subretinal gene therapy14 is not safe in infant eyes, and no commercially available medications specifically inhibit VEGF receptor-2 signaling only in retinal endothelial cells currently. However, clinical evidence of laboratory-based proof of concept is important. Therefore, we used the anti-VEGF agent, bevacizumab, administered bilaterally at the same dosages to a group of infants with type 1 ROP, and compared the effect on peripheral vascular extension to a group of infants with ROP less severe than type 1 ROP. We tested the hypothesis that effective intravitreal anti-VEGF treatment for type 1 ROP would extend vascularization into the peripheral avascular retina to a similar extent as the natural history of eyes with ROP that was less severe than type 1 and, therefore, did not receive anti-VEGF treatment. We matched the treatment and control groups for gestational age and birthweight. Retinal images of infants were taken by the same certified ophthalmic photographer using the same fundus camera and were analyzed by a different, masked reviewer. We also attempted to match baseline and follow-up images between treatment and control groups by post-gestational age (PGA) and analyzed the difference in vascular extension. Our study provides evidence that using an intravitreal anti-VEGF agent to regulate VEGF signaling extends vascularization into the peripheral avascular retina to a greater extent that what naturally occurs in an untreated suitable comparison group. We describe our approach to analyze retinal images that may be considered for future prospective clinical trials testing different anti-VEGF agents and doses.

METHODS

Patients

This study was approved by the University of Utah Institutional Review Board and adhered to the Declaration of Helsinki. All data and imaging were obtained through the University of Utah electronic medical record system. All premature infants screened for ROP (<30 weeks gestational age [GA), under 1500 g) at Primary Children’s Hospital and the University of Utah UHealth Hospital neonatal nurseries between January 2019 through December 2022 were included. At every examination, infants had dilated eye examinations with indirect ophthalmoscopy and contact fundus images taken by the same ophthalmic photographer (MC), who also was the ROP coordinator and assured follow-up examinations on all screened infants. Follow-up examinations were performed according to the recommendations of the AAO and AAP,18 and included retinal imaging. Infants were diagnosed as having no ROP or incomplete vasculature, any ROP less than type 1 ROP, or type 1 ROP (zone 1 or 2, stage 2 or 3, with plus disease or zone 1, stage 3 without plus).9

Confirmation of type 1 ROP was made by the same pediatric vitreoretinal specialist (MEH). Infants with type 1 ROP whose parents consented for anti-VEGF treatment with bevacizumab 0.25 mg19 and not laser were included. Gestational age-matched and birth weight-matched infants (within 50 grams of birth weight) with ROP less severe than type 1 ROP were included as controls. Figure 1 shows a flowchart of included infants.

Figure 1:

Figure 1:

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Flowchart of included patients.

Infants with Type 1 ROP had retinal examinations at the time of treatment and weekly thereafter. Control infants had examinations according to the AAO and AAP guidelines.18 All infants in the treatment group had regression of ROP following bevacizumab treatment with no reactivation between times of baseline and follow-up image acquisition (study period). After the study period, some infants received additional treatment with bevacizumab (n=1 for reactivation) or laser (n=4 for reactivation and n=1 for PAR). One eye in the treatment group first had bevacizumab for reactivation and later laser for PAR. No infant in the control group received intravitreal injections or laser during the study.

Retinal Imaging

As long as infants were medically stable, retinal imaging was performed within the 2 weeks prior to treatment and weekly thereafter for treated infants and weekly to every two weeks for control infants. All images were obtained with the same contact, fundus camera (Phoenix Icon, Neolight, 2018). The camera uses a fixed lens and angle of depth to ensure consistency between images. The angle from the center of the eye in radians times the radius provides the length along the periphery of the eye. The ICON has a 100 degree field of view or 1.75 radians. Clarification with Neolight was made and additionally confirmed by the masked analyst that pixels represented the same distance on different images from the same examination date and from longitudinal examination dates. For additional quality control to ensure images were comparable, the optic nerve diameter was measured at baseline and follow-up and found to be the same.

Image Analysis

Prior to analysis, all images of infants were de-identified by the ophthalmic photographer (MC) and assessed for quality while the analyst (LS) remained masked. Only infants with readable baseline and follow-up mages were included in the groups. Only one eye with the better imaging quality was included in analysis unless both eyes had similar imaging quality, and then the right eye was analyzed. Baseline images of eyes in the treatment group were avoided on the day of injection to reduce the risk of infection. Attempts were made to include imaging within one week prior to treatment but were allowed within a two-week time frame prior to injection to obtain adequate quality images for inclusion in the study. Because of the fragile nature of infants and difficulty obtaining high quality images at baseline and follow-up for analysis, baseline and follow-up images for control infants were also matched as close as possible to the PGAs of respective images of infant eyes in the treatment group.

Two images were obtained at baseline and follow-up, one from the posterior pole and one from the temporal retina, in order to measure the peripheral retinal vascular extent. The masked analyzer (LS) performed a test-retest on 10 randomly selected eyes and found excellent accordance (difference of less than 5%).

Retinal images and quantitative assessment of retinal vascular extent

The process of measuring vascular extent is shown in Figure 2. The posterior pole and temporal images of the same eye showed overlapping landmarks at retinal vascular bifurcations. Using Adobe Illustrator, a marking line was placed to identify landmarks in each image (black lines, D, Figure 2). The marking line was placed in baseline and follow-up images at the same location, based on the landmarks. The measurement line (white line, Figure 2) was placed at a 90-degree angle from the most temporal point of the optic nerve to the marking line in the posterior pole image. The measurement line was continued to the peripheral retinal vascular extent in the second image, at the same angle to ensure a direct extension of the first measurement line. To ensure accurate placement of lines and identical angles, lines were copied from the baseline image onto the follow-up image. The optic disc diameter was marked at each posterior pole image (line A, Figure 2). The extent from the optic nerve to the measurement line (line B, Figure 2) and the extent from the measurement line to the peripheral vascular extent (line C, Figure 2) were saved in Adobe Photoshop and later measured using the measurement tool. The total vascular extent was the sum of lines B and C. The temporal vascular extent included the width of the ROP ridge, if present. The diameter of the optic disc was also measured. All measurements were recorded in pixels (px), which can be converted to microns. The utilization of pixels as a measurement unit allows analysis of the posterior pole in a consistent way.

Figure 2:

Figure 2:

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Analysis of included eyes. A: Optic nerve diameter. B: Optic nerve to marking line. C: Marking line to peripheral edge of vasculature. D: Marking line.

Statistical analysis

SPSS 22 (SPSS Inc., Chicago, IL, USA) was used for all statistical analysis. Paired and unpaired two-sided t-tests were used to compare the vascular extent at baseline and follow-up between treatment and control infant eyes. A two-sided t-test was also used to compare the difference in vascular extension between the two groups.

RESULTS

Infants

Of 382 consecutive premature infants screened during the study period, 138 had incomplete vascularization and never developed ROP; 210 developed ROP less than type 1 ROP, and 34 developed type 1 ROP. Of the infants with type 1 ROP, 13 were consented for and received bilateral laser treatment. These infants were excluded from the study. The 21 remaining infants with type 1 ROP received bilateral bevacizumab. Of these, 4 were immediately excluded from analysis (1 passed away during the study period, and 3 received treatment at an outside hospital). An additional 6 patients were later excluded due to poor-quality images within the study period (e.g., poor pupillary dilatation precluding adequate imaging of optic nerve or the temporal periphery; media opacity, images failing to show full extent of retinal vasculature). Infant agitation interfering with image acquisition without general anesthesia was the main reason for poor image quality. Eleven infants met criteria of having images from at least one eye that included the peripheral temporal retina and the optic nerve. Eleven eyes from eleven matched infants with ROP less severe than type 1 ROP and who had adequate images were included in the control group. Eyes in the treatment group had ROP in zone I (n=1), posterior zone II (n=8) or mid to anterior zone II (n=2). Eyes in the control group had ROP in posterior zone II (n=2) or mid to anterior zone II (n=9). There were no significant differences in mean birth weight, GA, and PGA at time of baseline images between infants in the treatment and control groups. In addition, there was no significant difference in optic nerve size between baseline and follow-up images or between treatment and control groups (Table 1). Images of sufficient quality were analyzed at baseline and follow-up from treatment and control groups and the difference in vascularization between baseline and follow-up images is plotted in Figure 3.

Table 1:

Patient Characteristics

Control Treatment 95% CI P-value
Number included 11 11 NA NA
Birthweight in grams (g) 630 ± 92 629 ± 88 −81; 79 0.972
PGA at baseline image (weeks) 34.1 ± 3 34.8 ± 3 −1.9; 3.2 0.594
Gestational age (weeks) 24 ± 1 24 ± 1 −1; 4 0.363
Optic nerve size (pixels) 424 ± 121 434 ± 50 −76; 95 0.808
Baseline zones of ROP:
Zone I 0 1 NA NA
Posterior zone II 2 8 NA NA
Mid to Anterior zone II 9 2 NA NA
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Patient characteristics of control and treatment groups. CI: confidence interval, PGA: post-gestational age. Values are shown with ± standard deviation if applicable.

Figure 3:

Figure 3:

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Changes in vascular extension. A) Difference in peripheral vascular extent at baseline and follow-up. B) Difference in advancement of peripheral retinal vasculature.

Baseline retinal vascular extent in treatment and control groups

At baseline, there was a non-significant trend in peripheral retinal vascular extent between the treatment and control groups (p=0.084), with greater vascular extent in the control group. At follow-up, there was no significant difference in the peripheral vascular extent between treatment and control groups, suggesting catch-up growth (p=0.945, Table 2). Both groups showed a significant increase in retinal vascular extent from baseline to follow-up (p=0.0002).

Table 2:

Horizontal vascular extent from optic nerve

Control Treatment 95% CI of difference P-value
Baseline 4262 ± 937 3667 ± 547 −1277; 88 0.084
Follow-up 4514 ± 1009 4539 ± 612 −717; 767 0.945
Difference in vascular extent between baseline and follow-up (pixels) 253 ± 151 872 ± 521 262; 977 0.003
95% CI comparing difference in vascular extent between baseline and follow-up image (pixels) −354; −151 −1222; −522 NA NA
P-Value comparing difference in vascular extent between baseline and follow-up 0.0002 0.0002 NA NA
Difference in vascular extent divided by days between baseline and follow-up (pixels) 14 ± 11 47 ± 33 10; 56 0.008
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Changes in the horizontal vascular extent of control and treatment group. CI: Confidence interval. Values shown with ± standard deviation, if applicable.

Difference in peripheral retinal vascular extent between treatment and control groups

Vascular extent increased by a mean of 253 pixels in the control group, and a mean of 872 pixels in the treatment group (P<0.003). The mean increase in vascular extent divided by days was 14 pixels per day in the control group and 47 pixels per day in the treatment group (p-0.008; Table 2 and Figure 3). Although it is recognized this daily growth may not be linear since only the baseline and final visits were included when determining the value, the daily average provides a sense of the different cadence in growth between the two groups. Figure 4 highlights that it was not the days between baseline and follow-up image acquisition but the use of anti-VEGF that extended vascularization to a greater degree than the natural history of untreated eyes.

Figure 4:

Figure 4:

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Differences in vascular extension plotted against days between baseline and follow-up imaging for individual infant eyes shows that treated infants have greater vascular extension than controls.

The vascular extension from the optic nerve to the marking line (line B) was similar at baseline and follow-up with a difference of 4 ± 198 pixels in controls (P=0.955) and 23 ± 180 pixels in the treatment group (P=0.680). There also was no significant difference in the change of vascular extent from optic nerve to the marking line (line B) between treatment and control groups (P=0.746). However, the vascular extent increased significantly from the marking line to the peripheral edge of the retinal vasculature (line C) in both groups. Greater vascular extension from the marking line to the peripheral extent occurred in the treatment group (1845 ± 402 px at baseline to 2695 ± 714 px at follow-up, p=0.00096) compared with the control group (2382 ± 903 px at baseline to 2638 ± 1005 px at follow-up, p=0.016) (Figure 5, Table 3). There was also significantly greater vascular extension (P=0.011) in the treatment (849 ± 611 px) compared to the control group (256 ± 292 px).

Figure 5:

Figure 5:

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Differences in vascular extent between treatment and control groups. Difference from optic nerve to marking line, and marking line to vascular edge at baseline and follow-up.

Table 3:

Distances in vascular extent

Control Treatment CI of difference between groups P-value of difference between groups
Optic nerve to Marking Line (pixels, line B) Baseline 1880 ± 519 1821 ± 428 −482; 365 0.776
Follow-up 1876 ± 586 1845 ± 427 −488; 424 0.885
CI for difference of vascular extent within each group between baseline and follow-up −130; 137 −144; 98 NA NA
P-value for difference of vascular extent within each group between baseline and follow-up 0.955 0.680 NA NA
Marking Line to temporal vascular extent (pixels, line C) Baseline 2382 ± 903 1845 ± 402 −1158; 85 0.094
Follow-up 2638 ± 1055 2695 ± 714 −744; 857 0.884
95% CI for difference of vascular extent within each group −453; −60 −1259; −439 NA NA
P-Value for difference of vascular extent within each group between baseline and follow-up 0.016 0.00096 NA NA
Difference in vascular extent between baseline and follow-up (pixels, line B) 4 ± 198 23 ± 180 −142; 195 0.746
Difference in vascular extent between baseline and follow-up (pixels, line C) 256 ± 292 849 ± 611 156 px; 1030 0.011
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Distances in vascular extent. Values shown with ± standard deviation, if applicable.

DISCUSSION

Intravitreal anti-VEGF was used about 15 years ago for severe ROP and was first published in clinical trials about 12 years ago.20–22 Since then, few studies discuss vascularization of the peripheral avascular retina, whereas many describe persistent avascular retina (PAR) following anti-VEGF. Experimental data provided proof of concept that regulation of VEGF signaling,14 specifically through VEGF receptor-2 in retinal endothelial cells, allowed for ordered endothelial cell divisions with extension of linear intraretinal vessels toward the ora serrata rather than erratic growth as intravitreal neovascularization or stage 3 ROP.6,23,24 This laboratory-based evidence led to our clinical hypothesis that intravitreal anti-VEGF would change the cadence of peripheral developmental vascular growth. We designed a study that was controlled and masked to determine whether anti-VEGF facilitated vascularization of the peripheral avascular retina. This retrospective study included all consecutive premature infants screened for ROP at the same institution (UHealth/PCH) over approximately 3 years to investigate the effect of bilateral, single low-dose intravitreal injections of bevacizumab (0.25 mg) on peripheral retinal vascular extension compared to untreated gestational age- and birth-weight matched infants with non-treatment warranted ROP. We provide evidence that regulation of VEGF signaling, in this case using a broad intravitreal anti-VEGF agent, increases peripheral intraretinal vascular growth in type 1 ROP to a greater extent than the natural history of a suitable control group. We chose dose based on studies from the Pediatric Eye Disease Investigative Group (PEDIG).25 We believe it was not appropriate to have a control group of infants with type 1 ROP who were only observed, so we chose a comparison group of gestational age- and birthweight-matched infants with ROP less severe than type 1 ROP within the same time frame as the study period.

Although case studies and clinical trials studying anti-VEGF agents describe growth of vessels into the retinal periphery in ROP, to our knowledge, none has compared the growth after an anti-VEGF agent to a suitable control or comparison group. One other study quantified an increase in temporal retinal vascularization and supported the concept that inhibiting VEGF signaling would extend peripheral vascular growth. This study looked at short-term (7.3 weeks) and long-term (69.1 weeks) temporal vascularization after intravitreal bevacizumab. There was a significant extension of temporal vascularization in eyes with short-term follow-up. In 15 evaluated eyes, an increase of 3.6 ± 2.0 horizontal disc diameters was reported on average 7.3 weeks later, whereas growth was 5.1± 2.5 horizontal disc diameters at 69.1 weeks.26 However, only treated eyes were investigated, and no comparison group was included.

Treatments for ROP have included cryotherapy or laser ablation of peripheral avascular retina, and now intravitreal injections of anti-VEGF agents.9–13 Several multicenter clinical trials have reported efficacy with different anti-VEGF agents some of which have been approved for infants with ROP by the European Medicine Agency (EMA) or the Food and Drug Administration (FDA).11,12 Most treatments have focused on inhibiting aberrant intravitreal neovascularization (i.e., Stage 3 ROP), but fewer have focused on vascularizing the peripheral avascular retina, although experimental studies have been performed with this goal in mind for over a decade.15,27 With greater ability to examine the vasculature of the peripheral retina using wide field fluorescein angiography, the topic of persistent avascular retina (PAR) after anti-VEGF treatment has been discussed recently.28,29 It has been known that laser treatment to the peripheral avascular retina generally reduces vascularization into the periphery. In addition, peripheral avascular retina, before being termed PAR, has been recognized historically in adults who had regressed ROP or were premature and never received anti-VEGF. One study found that 91% of the 43 investigated eyes of patients who were initially screened for ROP but did not receive treatment had PAR.30 Our study provides strong evidence using a suitable control group that regulating VEGF using a neutralizing intravitreal antibody against VEGF facilitates vascularization of some of the peripheral avascular retina. Although complete vascularization may not occur in all infants, extension of vascularization temporally to some degree can potentially expand visual field and reduce the hypoxic stimulus from avascular retina that might lead to reactivation. It also remains unknown if certain agents or doses are more effective at extending peripheral retinal vascularization. Additional studies are needed to quantify effects of anti-VEGF agents at different doses or other treatments. We provide a quantitative approach that might be used for current clinical trials with adequate imaging or in future ones.

Our results show a significant difference in the temporal extension of vascular growth in treated infants with type 1 ROP than in controls suggesting catch-up growth as well as greater growth than the natural history of a suitable comparison group. After an anti-angiogenic agent, one might predict there to be a decrease in vascular growth peripherally as well as into the vitreous. It is striking that the growth of normal vasculature is accelerated by almost 5 times after a single injection of low-dose anti-VEGF in the initial post-injection period. One effect from anti-VEGF is the reduction in tortuosity and dilation of retinal vessels (i.e., plus disease). We wondered if the increase in peripheral vascular extension was due to straightening of the tortuous vessels. It was not possible to measure vascular lengths accurately, but the finding that there was no significant difference in extent from the optic disc to the marking line between the treatment and control groups and between baseline and follow-up supported the thinking that the temporal extension was not due only to straightening of tortuous vessels but actual vessel growth.

Strengths of this study are the inclusion of all infants screened for ROP at one center with adequate fundus imaging at baseline and follow-up visits. All consecutive preterm infants meeting criteria for screening for ROP were assessed, and the number of type 1 ROP infants was within expectations given the number of premature infants screened. Because a fixed lens and angle of depth was used in the camera, consistency between images and pixels representing vascular extent was ensured across all fundus images and longitudinally over visits. The same photographer, who was also the ROP coordinator, assured follow-up of all premature infants, and obtained and de-identified all images. Our image analyst was masked throughout the study for treatment and control groups. We do not recommend anti-VEGF for less severe ROP than type 1 ROP based on this study as we did not study these patients.

This study has limitations, the most important being small sample size. Future studies are important to test our hypothesis on larger patient samples. We did not use fluorescein angiography, which can provide information on vessel perfusion, and this is important in future studies. The retrospective nature of this study is another limitation, but we analyzed all consecutive infants in the study period in a controlled fashion.

In conclusion, this study provides quantification of clinically measured fundus images in support of experimental proof of concept that regulation of the VEGF receptor-2 pathway in endothelial cells not only inhibits pathologic angiogenesis, but also extends peripheral retinal vascularization in treated type 1 ROP compared to the natural history of a suitable comparison group of matched premature infants.

ACKNOWLEDGEMENTS

a. Funding/Support:

NIH R01 EY015130, R01 EY017011, R21 EY033579, R13 EY03517901 (to MEH); Achievement Rewards for College Scientists (ARCS) Scholarship, Utah ARCS Foundation (to LS); Departmental grants to University of Utah, Moran Eye Center, and to Stanford University, Byers Eye Institute, from Research to Prevent Blindness.

b. Financial Disclosures:

University of Utah received money to support IRB proposal from Regeneron in September, 2021

c. Other:

no writing, statistical, or expert contributions

Declaration of interests

Consultant for Janssen (J&J)

Non-paid board member for ARVO Foundation, Jack McGovern Coats’ Disease Foundation, and review grants for the Macula Society and the Knights Templar Eye Foundation

Biography

graphic file with name nihms-1954094-b0001.gif

Mary Elizabeth Hartnett, MD, is the Michael F. Marmor, M.D. Professor in Retinal Science and Diseases and is a Professor of Ophthalmology at Stanford University. Dr. Hartnett is the director of Pediatric Retina at Stanford University and principal investigator of a retinal angiogenesis laboratory, in which she studies causes and treatments for diseases including retinopathy of prematurity and age-related macular degeneration. She created the first-ever academic textbook on the subject, Pediatric Retina, in its third edition, which has proven to be an invaluable resource for residents and ophthalmologists internationally.

Footnotes

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Meeting presentation: Advances in Pediatric Retina Course 2023

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